Reviews & Analysis

In this Review, Besselink and colleagues discuss preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer, including disease staging and response evaluation.

In 2023, we witnessed advances in allocation policies and marginal donors, including living donors. Key improvements included the uncapped Model for End-stage Liver Disease 3.0 score, unveiled machine perfusion trials to standard deceased donors and lessons from the aborted living donor liver transplantations.

Enteric nervous system function is essential for survival. Studies published in 2023 have provided important novel insights into the mechanisms that regulate its development and maintenance, and demonstrate how it can be restored when these mechanisms fail.

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory disease (IMID). Here, the authors review evidence on the preclinical phase of IBD, outlining and describing the proposed at-risk, initiation and expansion phases. Overlap with other IMIDs is discussed alongside the possible future directions for research into preclinical IBD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a strong heritable component, and genome-wide association cohort studies are highlighting the major genetic determinants of this condition. A meta-analysis of these databases has now enabled expansion of the list of the inherited variants that modulate the risk of MASLD. The identification of new MASLD risk loci is improving comprehension of disease pathogenesis and individual risk stratification, and also enabling the identification of novel therapeutic targets and disease subtypes that might ultimately lead to a precision medicine approach.

Innovative approaches to increase testing are needed to achieve the 2030 hepatitis B and hepatitis C elimination targets. Zhang et al., partnering with local community organizations, successfully used a pay-it-forward approach to increase hepatitis B and hepatitis C testing among men who have sex with men in China.

Cirrhosis recompensation is gradually gaining traction, but a definition for recompensation in nonalcoholic fatty liver disease (NAFLD)-related cirrhosis is currently lacking. This Perspective provides an overview of the natural history of NAFLD and discusses NAFLD-related cirrhosis recompensation.

The incidence of pancreatic ductal adenocarcinoma (PDAC) is rising. In this Review, Hu and O’Reilly summarize the latest advances and clinical trials for the treatment of PDAC, including biomarkers, targeted therapies and immunotherapy as well as novel clinical trial designs. They also discuss emerging therapeutic options for this disease.

This Perspective explores the relationship between screening endoscopy and colorectal cancer incidence, examining available evidence and offering insights into the discrepancies between real-world and trial evidence alongside potential pitfalls with interpreting the data.

Histological assessment of nonalcoholic fatty liver disease (NAFLD) is essential for clinical practice as it outlines diagnosis and lays the foundation of medical care. This Perspective summarizes the advancements in digital histology and discusses current and future applications in NAFLD.

In this Expert Recommendation, Uhlig and colleagues review the therapeutic landscape for monogenic inflammatory bowel disease and propose recommendations for standardized reporting of clinical outcomes.

In this Review, Murphy and Zaki discuss changes in the incidence and mortality of colorectal cancer, including trends by age and birth cohort, and consider the contributions of early-life exposures and emerging risk factors.

Increasing evidence shows a role of cellular stress responses in nonalcoholic steatohepatitis (NASH) and liver fibrosis pathogenesis. This Review provides a comprehensive overview of the molecular mechanisms involved in cellular stress in fibrogenesis and their role in NASH progression.

Hormones released in the gut orchestrate pivotal physiological processes. In this Review, the authors present an overview of gut hormones that are involved in the regulation of metabolism, and discuss their action in the gastrointestinal system and beyond.

In this Review, Arrese and colleagues discuss the intersection of nonalcoholic fatty liver disease and alcohol-related liver disease, including their pathophysiology, clinical management and suggestions for future research.

Hepatic stellate cells (HSCs) drive liver fibrosis and are closely linked to liver cancer development. This comprehensive Review provides an in-depth analysis of the specific characteristics of HSCs in cancer, highlighting therapeutic implications based on progress in clarifying HSC biology.

In this Review, Huang et al. discuss the current status of hepatocellular carcinoma surveillance, the remaining challenges, including the changing aetiology of liver disease, and strategies to improve the utilization and quality of surveillance.

The importance of commensal fungi in health and disease is becoming increasingly clear. In this Review, Ost and Round discuss the involvement of the mycobiota in intestinal diseases, and consider potential opportunities to target fungi and their interactions for therapeutic purposes.

Nonalcoholic fatty liver disease (NALFD) prevalence, including in children and adolescents, is rising worldwide. This Review offers a comprehensive overview of the lifestyle interventions available for NAFLD, including dietary and physical-activity strategies.

Liver inflammation is a key process that orchestrates intrahepatic injury. This Review offers a comprehensive overview of the inflammatory mechanisms of hepatic fibrosis and discusses current advances and therapeutic implications.